2-120349274-C-T

Position:

• chr2-120349274-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002193.4(INHBB):​c.624C>T​(p.His208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 1,614,078 control chromosomes in the GnomAD database, including 5,989 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.065 (762 hom., cov: 33)
  • Exomes 𝑓: 0.055 (5227 hom.)
• Consequence: INHBB NM_002193.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884

Genes affected

INHBB (HGNC:6067): (inhibin subunit beta B) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate a subunit of the dimeric activin and inhibin protein complexes. These complexes activate and inhibit, respectively, follicle stimulating hormone secretion from the pituitary gland. Polymorphisms near this gene are associated with pre-eclampsia in female human patients. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.884 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INHBB	NM_002193.4	c.624C>T	p.His208=	synonymous_variant	2/2	ENST00000295228.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INHBB	ENST00000295228.4	c.624C>T	p.His208=	synonymous_variant	2/2	1	NM_002193.4	P1

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9936 AN: 152096 Hom.: 757 Cov.: 33

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.0589

Gnomad FIN AF: 0.0657

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0363

Gnomad OTH AF: 0.0556

GnomAD3 exomes AF: 0.0901 AC: 22649 AN: 251440 Hom.: 2538 AF XY: 0.0819 AC XY: 11125 AN XY: 135914

Gnomad AFR exome AF: 0.0500

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.0109

Gnomad EAS exome AF: 0.409

Gnomad SAS exome AF: 0.0493

Gnomad FIN exome AF: 0.0645

Gnomad NFE exome AF: 0.0354

Gnomad OTH exome AF: 0.0668

GnomAD4 exome AF: 0.0547 AC: 79942 AN: 1461864 Hom.: 5227 Cov.: 31 AF XY: 0.0536 AC XY: 39008 AN XY: 727240

Gnomad4 AFR exome AF: 0.0448

Gnomad4 AMR exome AF: 0.194

Gnomad4 ASJ exome AF: 0.0117

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.0518

Gnomad4 FIN exome AF: 0.0605

Gnomad4 NFE exome AF: 0.0383

Gnomad4 OTH exome AF: 0.0628

GnomAD4 genome AF: 0.0653 AC: 9946 AN: 152214 Hom.: 762 Cov.: 33 AF XY: 0.0708 AC XY: 5268 AN XY: 74408

Gnomad4 AFR AF: 0.0481

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.0589

Gnomad4 FIN AF: 0.0657

Gnomad4 NFE AF: 0.0363

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0291 Hom.: 37

Bravo AF: 0.0753

Asia WGS AF: 0.189 AC: 657 AN: 3478

EpiCase AF: 0.0333

EpiControl AF: 0.0327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4328642; hg19: chr2-121106850; COSMIC: COSV54677544;